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A metatranscriptomic approach to explore longitudinal tissue specimens from non-healing diabetes related foot ulcers


Cellular mechanisms and/or microbiological interactions which contribute to chronic diabetes related foot ulcers (DRFUs) were explored using serially collected tissue specimens from chronic DRFUs and control healthy foot skin. Total RNA was isolated for next-generation sequencing. We found differentially expressed genes (DEGs) and enriched hallmark gene ontology biological processes upregulated in chronic DRFUs which primarily functioned in the host immune response including: (i) Inflammatory response; (ii) TNF signalling via NFKB; (iii) IL6 JAK-STAT3 signalling; (iv) IL2 STAT5 signalling and (v) Reactive oxygen species. A temporal analysis identified RN7SL1 signal recognition protein and IGHG4 immunoglobulin protein coding genes as being the most upregulated genes after the onset of treatment. Testing relative temporal changes between healing and non-healing DRFUs identified progressive upregulation in healed wounds of CXCR5 and MS4A1 (CD20), both canonical markers of lymphocytes (follicular B cells/follicular T helper cells and B cells, respectively). Collectively, our RNA-seq data provides insights into chronic DRFU pathogenesis.

Type Journal
ISBN 1600-0463 (Electronic) 0903-4641 (Linking)
Authors Radzieta, M.; Peters, T. J.; Dickson, H. G.; Cowin, A. J.; Lavery, L. A.; Schwarzer, S.; Roberts, T.; Jensen, S. O.; Malone, M.
Publisher Name APMIS
Published Date 2022-07-31
Published Volume 130
Published Issue 7
Published Pages 383-396
Status Published in-print
DOI 10.1111/apm.13226
URL link to publisher's version